Early detection of breast cancer reduces mortality. Contrast-enhanced Magnetic Resonance Imaging (MRI) is recommended for screening women at high risk for breast cancer because it is nearly twice as sensitive as X- ray mammography. Unfortunately, intravenous gadolinium-based contrast agents substantially increase the costs and potential risks of MRI. Our goal is effective breast MRI screening without IV contrast agents. The most promising approach for non-contrast breast MRI is diffusion-weighted imaging (DWI). Echo-planar imaging (EPI-) DWI reveals tumors because increased cellular density and altered microscopic structure restrict water diffusion. However, EPI-DWI suffers from low resolution and distortions due to magnetic field variations in the breast. We aim to create a robust alternative based on double echo in steady-state (DESS) imaging: First, we will develop and optimize the DESS-DWI technique. We will develop accurate signal models that use signal information in both DESS echoes to maximize diffusion weighting and to minimize sensitivity to confounding factors. We will modify data acquisition to correct motion artifacts, and develop post-processing methods to generate T2-weighted images and diffusion maps from two interleaved DESS-DWI acquisitions. Second, we will test DESS-DWI in patients. We propose to compare the sensitivity of DESS-DWI with X-ray mammography, standard EPI-DWI and DCE-MRI in patients undergoing clinical MRI for high-risk screening or breast cancer evaluation. We will compare the biopsy rate precipitated by DESS-DWI with that of standard DCE-MRI in the subgroup of patients who underwent MRI for high-risk screening. This will be the first use of steady-state diffusion-weighted MRI for breast cancer. The proposed DESS-DWI technique has several novel features. It offers 3D scanning with high spatial resolution to show morphologic features in detail. It provides both T2 imaging and diffusion sensitivity in a single 3D sequence with better accuracy than previous steady-state diffusion methods. It avoids the distortions of EPI-DWI, offering unprecedented ability to perform multiparametric, pixel-by-pixel analysis and correlation with other sequences. At the conclusion of this work, we will have developed and tested a new gadolinium-free approach for high-risk breast cancer screening. Future clinical validation of these techniques could make screening breast MRI available to a broader population and thus improve early detection and treatment of breast cancer. PUBLIC HEALTH RELEVANCE: The goal of this project is to create an accurate magnetic resonance imaging (MRI) technique for detecting breast cancer that does not require an intravenous injection of contrast material. The approach is to develop and test a three-dimensional, high-resolution, distortion-free pulse sequence that reveals the substantially restricted diffusion of water in tumors. Eliminating gadolinium contrast material will reduce the duration, cost, risk and invasiveness of breast MRI, enabling MRI to be used more widely to screen for occult, early-stage, treatable breast cancer.